rs12592307

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000275.3(OCA2):c.2364G>A(p.Ser788Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,612,506 control chromosomes in the GnomAD database, including 46,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4160 hom., cov: 32)

Exomes 𝑓: 0.22 ( 42014 hom. )

Consequence

OCA2
NM_000275.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.606

Publications

25 publications found

Variant links:

Genes affected

OCA2 (HGNC:8101): (OCA2 melanosomal transmembrane protein) This gene encodes the human homolog of the mouse p (pink-eyed dilution) gene. The encoded protein is believed to be an integral membrane protein involved in small molecule transport, specifically tyrosine, which is a precursor to melanin synthesis. It is involved in mammalian pigmentation, where it may control skin color variation and act as a determinant of brown or blue eye color. Mutations in this gene result in type 2 oculocutaneous albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

OCA2 Gene-Disease associations (from GenCC):

oculocutaneous albinism type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, ClinGen

OCA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 15-27845027-C-T is Benign according to our data. Variant chr15-27845027-C-T is described in ClinVar as Benign. ClinVar VariationId is 255730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.606 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3 link	c.2364G>A	p.Ser788Ser	synonymous_variant	Exon 23 of 24	ENST00000354638.8	NP_000266.2	Q04671-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8 link	c.2364G>A	p.Ser788Ser	synonymous_variant	Exon 23 of 24	1	NM_000275.3	ENSP00000346659.3		Q04671-1
OCA2	ENST00000353809.9 link	c.2292G>A	p.Ser764Ser	synonymous_variant	Exon 22 of 23	1		ENSP00000261276.8		Q04671-2

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31785

AN:

151700

Hom.:

4157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.563

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.212

GnomAD2 exomes

AF:

0.277

AC:

69666

AN:

251336

AF XY:

0.274

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.449

Gnomad ASJ exome

AF:

0.320

Gnomad EAS exome

AF:

0.564

Gnomad FIN exome

AF:

0.240

Gnomad NFE exome

AF:

0.198

Gnomad OTH exome

AF:

0.261

GnomAD4 exome

AF:

0.223

AC:

325647

AN:

1460688

Hom.:

42014

Cov.:

AF XY:

0.225

AC XY:

163383

AN XY:

726708

show subpopulations

African (AFR)

AF:

0.101

AC:

3381

AN:

33470

American (AMR)

AF:

0.435

AC:

19457

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

8473

AN:

26124

East Asian (EAS)

AF:

0.586

AC:

23266

AN:

39686

South Asian (SAS)

AF:

0.312

AC:

26875

AN:

86206

European-Finnish (FIN)

AF:

0.232

AC:

12367

AN:

53416

Middle Eastern (MID)

AF:

0.267

AC:

1539

AN:

5766

European-Non Finnish (NFE)

AF:

0.194

AC:

215820

AN:

1110956

Other (OTH)

AF:

0.240

AC:

14469

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

11934

23869

35803

47738

59672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7860

15720

23580

31440

39300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.209

AC:

31805

AN:

151818

Hom.:

4160

Cov.:

AF XY:

0.219

AC XY:

16240

AN XY:

74182

show subpopulations

African (AFR)

AF:

0.111

AC:

4576

AN:

41362

American (AMR)

AF:

0.332

AC:

5066

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

1087

AN:

3468

East Asian (EAS)

AF:

0.563

AC:

2901

AN:

5152

South Asian (SAS)

AF:

0.311

AC:

1494

AN:

4804

European-Finnish (FIN)

AF:

0.255

AC:

2677

AN:

10506

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.193

AC:

13099

AN:

67942

Other (OTH)

AF:

0.213

AC:

449

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1173

2346

3518

4691

5864

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.203

Hom.:

5022

Bravo

AF:

0.214

Asia WGS

AF:

0.416

AC:

1446

AN:

3478

EpiCase

AF:

0.216

EpiControl

AF:

0.209

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Jun 20, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Tyrosinase-positive oculocutaneous albinism

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.11

(source)

DANN

Benign

0.54

PhyloP100

-0.61

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over